TRIM22 orchestrates the proliferation of GBMs and the benefits of TMZ by coordinating the modification and degradation of RIG-I.

Autor:	Fei X; Department of Neurosurgery, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710032, China., Wu X; Department of Neurosurgery, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710032, China., Dou YN; Department of Neurosurgery, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710032, China., Sun K; Department of Neurosurgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China., Guo Q; Department of Neurosurgery, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710032, China., Zhang L; Department of Neurosurgery, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710032, China., Li S; Department of Neurosurgery, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710032, China., Wei J; Department of Neurosurgery, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710032, China., Huan Y; Department of Neurosurgery, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710032, China., He X; Department of Neurosurgery, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710032, China., Fei Z; Department of Neurosurgery, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710032, China.
Jazyk:	angličtina
Zdroj:	Molecular therapy oncolytics [Mol Ther Oncolytics] 2022 Aug 25; Vol. 26, pp. 413-428. Date of Electronic Publication: 2022 Aug 25 (Print Publication: 2022).
DOI:	10.1016/j.omto.2022.08.007
Abstrakt:	Tripartite motif 22 (TRIM22) is an agonist of nuclear factor κB (NF-κB) that plays an important role in the proliferation and drug sensitivity of glioblastoma (GBM). However, the molecular mechanism underlying the protein network between TRIM22 and nuclear factor κB (NF-κB) in GBM remains unclear. Here, we found that knockout of TRIM22 effectively inhibited tumor proliferation and increased the sensitivity of GBM cells to temozolomide (TMZ) in vivo and in vitro . Moreover, TRIM22 forms a complex with cytosolic purine 5-nucleotidase (NT5C2) in GBM and regulates the ubiquitination of retinoic acid-inducible gene-I (RIG-I). TRIM22 promotes the K63-linked ubiquitination of RIG-I, while NT5C2 is responsible for K48-linked ubiquitination. This regulation directly affects the RIG-I/NF-κB/cell division cycle and apoptosis regulator protein 1 (CCAR1) signaling axis. Ubiquitin modification inhibitor of RIG-I restores the inhibition of tumor growth induced by TRIM22 knockout. The follow-up results showed that compared with patients with high TRIM22 expression, patients with low TRIM22 expression had a longer survival time and were more sensitive to treatment with TMZ. Our results revealed that the TRIM22-NT5C2 complex orchestrates the proliferation of GBM and benefits of TMZ through post-translational modification of RIG-I and the regulation of the RIG-I/NF-κB/CCAR1 pathway and is a promising target for single-pathway multi-target therapy. Competing Interests: The authors declare that they have no competing interests. (© 2022 The Author(s).)
Databáze:	MEDLINE
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